EP1017362B1 - Fluorid enthaltende zahnpasten mit verbesserte wirksamkeit - Google Patents

Fluorid enthaltende zahnpasten mit verbesserte wirksamkeit Download PDF

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Publication number
EP1017362B1
EP1017362B1 EP98946075A EP98946075A EP1017362B1 EP 1017362 B1 EP1017362 B1 EP 1017362B1 EP 98946075 A EP98946075 A EP 98946075A EP 98946075 A EP98946075 A EP 98946075A EP 1017362 B1 EP1017362 B1 EP 1017362B1
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Prior art keywords
compound
dentifrice
fluoride
component
weight
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Expired - Lifetime
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EP98946075A
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English (en)
French (fr)
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EP1017362A1 (de
Inventor
Yun Po Zhang
Abdul Gaffar
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Colgate Palmolive Co
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Colgate Palmolive Co
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/20—Halogens; Compounds thereof
    • A61K8/21—Fluorides; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a multicomponent anticaries dentifrice composition and method of use therefore, having a first component containing a fluoride ion source, and a second component containing a casein glycomacropeptide and, more particularly, to such a composition which exhibits enhanced anticaries and remineralization efficacy over like dentifrice compositions containing fluoride alone.
  • dental caries are caused by the production of acid by certain specific bacteria, such as streptococcus mutans. Repeated cycles of such acid attack results in microscopic demineralization or decalcification of the hydroxyapatite structure of the tooth enamel and the formation of an incipient carious lesion.
  • saliva provides a continuing source of calcium and phosphate to the tooth enamel which tends to remineralize the hydroxyapatite structure of the enamel, inhibiting and reversing the demineralizing carious process.
  • Casein glycomacropeptides which are natural ingredients of lactic origin, have been identified by the art to be effective antibacterial agents against microorganisms responsible for dental plaque and caries when applied to the tooth and periodontium, which is the investing and supporting tissue surrounding the tooth (i.e. the periodontal ligament, the gingiva, and the alveolar bone).
  • CGMP Casein glycomacropeptides
  • U.S. Patents 4,992,420 and 4,994,441 disclose that casein phosphopeptides derived from kappa-casein are effective for inhibiting the growth of streptococcus mutans, a bacteria species associated with dental caries and plaque formation.
  • CGMP agents at concentrations of 5% by weight, are over 20% less effective than the 1100 ppm fluoride ion as NaF generally available within commercial dentifrices.
  • fluoride-providing compounds are safe and effective anticaries agents which promote the remineralization process.
  • FDA U.S. Food and Drug Administration
  • the present invention encompasses a multicomponent dentifrice composition and use of the composition for the manufacture of a medicament for enhancing the remineralization and resultant anticaries efficacy of fluoride dentifrices.
  • the composition having a first dentifrice component containing a fluoride ion releasing compound and a second dentifrice component containing a casein glycomacropeptide compound; the first and second components being separated prior to use and when combined, upon application to the teeth, the dentifrice provides unexpectedly, significantly enhanced enamel remineralization and over that of either component independently, as will be hereinafter demonstrated.
  • the components of the multicomponent dentifrice of the present invention comprise a first fluoride ion releasing compound containing dentifrice component, and a second casein glycomacropeptide containing dentifrice component which may conveniently be combined in approximately equal weight proportions, so that only about one-half of the concentration of any particular ingredient within either component will be present when the components are combined and applied to the teeth, as by brushing.
  • the formulations for each component provides rheological characteristics so that each component is delivered in the desired predetermined amount, by extrusion from a dual compartmented tube or pump device.
  • the respective fluoride ion releasing compound or casein glycomacropeptide containing compound is incorporated within a dentifrice vehicle suitable for use in the oral cavity, which contains water, humectant, surface active agent and a polishing agent or abrasive.
  • the humectant is generally a mixture of humectants, such as glycerol, sorbitol and polyethylene glycol of a molecular weight in the range of 200-1000, but other mixtures of humectants and single humectants may also be employed.
  • the humectant content within each of the two components is in the range about of 15% to about 40% by weight and preferably about 20 to about 30% by weight.
  • the water content is from about 30% to about 60%, and preferably about 45% by weight.
  • the surface active agent aids in the thorough dispersion of the dentifrice throughout the oral cavity when applied thereto, as well as, improve the dentifrice's cosmetic acceptability and the foaming properties.
  • Surface active agents which can be included within the vehicle of each of the dentifrice components of the present invention, include anionic, nonionic or ampholytic compounds; anionic compounds being preferred.
  • Suitable surfactants include salts of the higher alkyl sulfates, such as sodium lauryl sulfate or other suitable alkyl sulfates having 8 to 18 carbon atoms in the alkyl group; sodium lauryl sulfoacetate, salts of sulfonated monoglycerides of higher fatty acids, such as sodium coconut monoglyceride sulfonate or other suitable sulfonated monoglycerides of fatty acids of 10 to 18 carbon atoms; salts of amides of higher fatty acid, e.g., 12 to 16 carbon atom acids, with lower aliphatic amino acids, such as sodium-N-methyl-N-palmitoyl tauride, sodium N-lauroyl-, N-myristoyl- and N-palmitoyl sarcosinates; salts of the esters of such fatty acids with isotonic acid or with glycerol monosulfate, such as the sodium salt of mono
  • alkene sulfonates or alkene sulfonates or mixtures thereof having 12 to 16 carbon atoms in the carbon chain of the molecule and soaps of higher fatty acids, such as those of 12 to 18 carbon atoms, e.g., coconut fatty acids.
  • the cation of the salt may be sodium, potassium or mono-, di or triethanol amine.
  • the quantity of surface active agent present within the various components of the present invention totals from about 0.5 to about 3.0% by weight, preferably about 0.8 to about 2.5% by weight of the combined multiple components.
  • Polishing agents or abrasives which may be incorporated in the dentifrice vehicle of each component, include sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate, aluminum silicate, calcined alumina, bentonite or siliceous materials or combinations thereof.
  • these materials are interactive with CGMP and should not be included in the CGMP dentifrice component.
  • siliceous materials which are not interactive with CGMP and therefore may be formulated in any of the dentifrice components.
  • a preferred siliceous polishing agent is a silica having a mean particle size up to about 20 microns; including a precipitated amorphous hydrated silica available under the trademark of Zeodent 115, from J.M. Huber Chemicals Division, Havre de Grace, Maryland 21078, or available under the trademark of Sylodent 783 from Grace Davidson, Baltimore, Maryland 21203.
  • polishing agent in generally comparable quantities in each of the components. Accordingly, as stated above, a siliceous polishing agent which will not interact with CGMP is preferred in each component of the present invention, at a concentration from about 10 to about 30% by weight, and preferably 15 to about 25% by weight of each component.
  • the first, fluoride ion containing dentifrice component contains a water-soluble fluoride compound as a source for releasing fluoride ions.
  • the fluoride compound may be in an amount sufficient to release a fluoride ion concentration in the composition at 25°C, and/or when it is used, from about 0.025% (or 250 ppm) to about 1% by weight (or 10,000 ppm), preferably from about 0.04% (or 400 ppm) to about 0.15% by weight (or 1,500 ppm), to provide the desired anticaries efficacy.
  • fluoride ion releasing materials can be employed as sources of water-soluble fluoride in the present invention including sodium fluoride, potassium fluoride, sodium monofluorophosphate and sodium hexafluorosilicate among others.
  • Sodium monofluorophosphate and sodium fluoride are particularly preferred, as well as mixtures thereof.
  • the second, CGMP containing dentifrice component of the present invention is maintained physically separate from the fluoride containing dentifrice component prior to use.
  • the CGMP containing component has within its dentifrice vehicle a casein glycomacropeptide compound, such as those identified in US Patent 4,992,420 as kappa-caseino glycomacropeptides and desialyated derivatives thereof.
  • kappa-caseino glycopeptides includes within its meaning a caseino glycopeptide, which is the water-soluble component emanating from the hydrolysis of kappa-casein with rennin, and a caseino-glycopeptide obtained by proteolysis of caseino-macroglycopeptide. Desialylated derivatives are obtained from caseino glycopeptides by more or less complete elimination of the sialic acids, i.e. N-acetylneuraminic and N-glycollylneuraminic acids, from the oligosaccharide chains of the caseino glycopeptide.
  • sialic acids i.e. N-acetylneuraminic and N-glycollylneuraminic acids
  • U.S. 4,992,420, and U.S. 5,075,424 which are incorporated herein by reference.
  • the method disclosed within U.S. 5,075,424 comprises adjusting the pH of a solution of milk starting materials (i.e. cheese whey), by the addition of an acid, such as hydrochloric, sulfuric, acetic, lactic, or citric acid; ultracentrafiltering the pH adjusted whey with a membrane having a molecular weight cut-off of 10,000 to 50,000; and collecting the filtrate which contains the desired kappa-caseino-glycopeptides.
  • an acid such as hydrochloric, sulfuric, acetic, lactic, or citric acid
  • ultracentrafiltering the pH adjusted whey with a membrane having a molecular weight cut-off of 10,000 to 50,000 and collecting the filtrate which contains the desired kappa-caseino-glycopeptides.
  • the CGMP is incorporated in the oral composition of the present invention at a concentration of about 2 to about 15% by weight, and preferably at about 8 to about 12% by weight of the CGMP component.
  • CGMP may be inactivated by the presence of anionic surfactants, to avoid any such biological inactivation of the CGMP by the surface active agent when anionic surfactants are used in the preparation of the CGMP containing dentifrice, a hydrolyzed protein compound is included in the dentifrice composition.
  • Useful protein compounds include hydrolyzed collagen proteins, specifically positively charged hydrolyzates containing high concentrations of basic amino acids obtained by extraction from a partially hydrolyzed collagen faction and isolation by ion exchange treatment with an anion exchange resin or a partially charged hydrolyzed collagen protein. Such hydrolyzed collagen proteins are known to the art and are more fully described in U.S. 4,391,798.
  • hydrolyzed collagen proteins include Crotein Q® , a quaternary derivative of hydrolyzed collagen protein available commercially from Croda Inc., New York, New York. Crotein Q has a minimum pH of 9.5-10.5, is an off-white, free-flowing powder and its adopted name is steartrimonium hydrolyzed animal protein.
  • gelatin food grade
  • hydrolyzed collagen protein prepared by boiling animal parts such as skin, tendons, ligaments and bones with water.
  • the presence of about 0.1 to about 2.5% by weight of the hydrolyzed protein compound in the casein glycomacropeptide component of the oral composition of the present invention is sufficient to inhibit any biological inactivation of the casein glycomacropeptide caused by contact with the anionic surfactant.
  • glycomacropeptide compounds are slightly acidic in nature and it is desired that the pH of each component of the dentifrice of the present invention be generally in a neutral range, preferably between pH 6.7 and pH 7.2, a basic buffering agent may be required.
  • the preferred buffering agent is sodium hydroxide, which is added in a quantity to obtain the desired neutral pH.
  • An optional ingredient within the casein glycomacropeptide component of the dentifrice composition of the present invention is a preservative to prevent microbial growth within the component.
  • Suitable preservatives include methylparaben, propylparaben, and benzoates such as sodium benzoate.
  • the quantity of such preservatives generally is from about 0 to about 5%, preferably from about 0.1% to about 2% by weight of the component.
  • Inorganic or organic thickeners may be included in the components of the multicomponent dentifrice of the present invention.
  • Organic thickeners include natural and synthetic gums and colloids such as carrageenan (Irish moss), xanthan gum and sodium carboxymethyl cellulose, starch, polyvinylpyrrolidone, hydroxyethylpropyl cellulose, hydroxybutyl methyl cellulose, hydroxypropylmethyl cellulose, and hydroxyethyl cellulose.
  • Inorganic thickeners are preferred and include amorphous silica compounds which function as thickening agents such as, colloidal silica compounds available under tradenames such as Cab-o-sil fumed silica from Cabot Corporation and distributed by Lenape Chemical, Bound Brook, New Jersey, Zeodent 165 from J.M. Huber Chemicals Division, Havre de Grace, Maryland 21078, and Sylox 15 from Grace Davidson, Baltimore, Maryland 21203.
  • Either inorganic or organic thickening agents, or combinations thereof, may be present in both components of the instant dentifrice in proportions of about 0.1 to about 5% by weight, preferably about 0.4 to about 2% in each of the two components of the instant dentifrice.
  • a striped dentifrice product may be obtained using the multicomponent dentifrice of the present invention, wherein colorants of contrasting colors are incorporated in each of the dentifrice components to be dispensed; the colorants being pharmacologically and physiologically nontoxic when used in the suggested amounts.
  • Colorants used in the practice of the present invention include both pigments and dyes.
  • Pigments used in the practice of the present invention include nontoxic, water insoluble inorganic pigments such as titanium dioxide and chromium oxide greens, ultramarine blues and pinks and ferric oxides as well as water insoluble dye lakes prepared by extending calcium or aluminum salts of FD&C dyes on alumina such as FD&C Green #1 lake, FD&C Blue #2 lake, FD&C R&D #30 lake and FD&C # Yellow 15 lake.
  • the concentration of the pigment or dye useful in each component of the dentifrice composition is from about 0 to about 2 percent by weight of the respective component and preferably from about 0.05 to about 0.5 percent by weight of the respective component.
  • antibacterial agents include antibacterial agents, antitartar actives, sweeteners and/or flavors.
  • Particularly preferred antibacterial agents are noncationic antibacterial agents based on phenolic and bisphenolic compounds, halogenated diphenyl ethers such as triclosan, benzoate esters and carbanilides.
  • Such antibacterial agents can be present in quantities from about 0.03 to about 1% by weight of the particular component.
  • noncationic antibacterial agents When noncationic antibacterial agents are included in any of the dentifrice components, there is also preferably included from about 0.05 to about 5% of an antibacterial enhancing agent (AEA) which enhances the delivery and retention of the noncationic antibacterial agent to, and retention thereof on oral surfaces.
  • AEA antibacterial enhancing agent
  • Patents 5,188,821 and 5,192,531 include synthetic anionic polymeric polycarboxylates, in the form 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether/maleic anhydride having a molecular weight (M.W.) of about 30,000 to about 1,000,000, most preferably about 30,000 to about 800,000.
  • M.W. molecular weight
  • These copolymers are available for example as Gantrez, e.g. AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97 Pharmaceutical Grade (M.W. 700,000) available from ISP Technologies, Inc., Bound Brook, N.J. 08805.
  • Antitartar actives such as tetrapotassium or tetrasodium pyrophosphates can be present in concentrations from about 0.5 to about 8% by weight of the particular component.
  • the sweetener will normally be that of an artificial or synthetic sweetener and the normal proportion thereof present will be in the range of 0.1 to 1% by weight of the respective component, preferably 0.2 to 0.5% by weight the respective component.
  • the flavor content which is preferably of a mixed peppermint/menthol flavor, will usually be in the range of 0.5 to 2% by weight of the respective component, preferably 0.5 to 1.0% by weight of the respective component.
  • the contents of any other components or adjuvants will normally not exceed 10% by weight, often will be less than 5% by weight, and can be as low as 0%.
  • the humectants e.g. glycerin, propylene glycol, polyethylene glycol ingredients
  • any sweetener and water in a conventional mixer, until the mixture becomes a homogeneous gel phase.
  • a pigment such as TiO 2
  • preservative such as sodium benzoate, any antibacterial agent such as triclosan, any antibacterial enhancing agent such as Gantrez, any tartar control agents such as tetrasodium pyrophosphate or sodium tripolyphosphate, any fluoride salt such as sodium fluoride, and/or casein glycomacropeptide anticaries agents.
  • preservative such as sodium benzoate
  • any antibacterial agent such as triclosan
  • any antibacterial enhancing agent such as Gantrez
  • any tartar control agents such as tetrasodium pyrophosphate or sodium tripolyphosphate
  • any fluoride salt such as sodium fluoride
  • casein glycomacropeptide anticaries agents are mixed until a homogen
  • the pH of the resultant mix is then adjusted using a basic buffering solution such as a 50% solution of sodium hydroxide. Thereafter any hydrolyzed protein compound and the thickener, flavor and surfactant ingredients are separately added and dispersed into a final mix; the final mix is agitated at high speed under vacuum of from about 20 to 100 mm of Hg.
  • the resultant product is in each case a homogeneous, semi-solid, extrudable paste product.
  • the multicomponent dentifrice composition of the present invention is packaged in a suitable dispensing container in which the components are maintained physically separated and from which the separated components may be dispensed synchronously as a ribbon for application to a toothbrush.
  • a suitable dispensing container in which the components are maintained physically separated and from which the separated components may be dispensed synchronously as a ribbon for application to a toothbrush.
  • Such containers are known in the art.
  • An example of such a container is a two compartment dispensing container, such as a pump or tube, having collapsible sidewalls, as disclosed in U.S. 4,487,757 and 4,687,663; wherein, the container body is formed from a collapsible plastic web and is provided with a partition within the container body defining separate compartments in which the physically separated components are stored and from which they are dispensed through a suitable dispensing outlet.
  • Toothpaste I a two component composition of the present invention, designated Toothpaste I.
  • the ingredients of each of the two components of Toothpaste I are itemized in Table I, below.
  • Toothpaste I which contained 5% CGMP and 1100 ppm F, when the individual components stored in a dual compartmentalized container were extruded synchronously and combined immediately prior to use, was evaluated in vivo for remineralization efficacy using the surface microhardness methodology described in Zhang et al, Journal of Clinical Dentistry, 6:148-153 (1995). The study was conducted as a randomized, cross-over, double-blind study with 12 healthy adults. Enamel demineralization of bovine enamel blocks was achieved in vitro by covering the bovine enamel blocks with glucan containing Streptococcus mutans Ingbritt-1600 serotype C, which was then exposed to a 25% sucrose solution for 2 hours at 37°C.
  • the adult subjects were fitted with oral maxillary palatal retainers, each holding four demineralized enamel blocks.
  • the subjects brushed their teeth for 30 seconds with 1.5 grams of Toothpaste I, swished for an additional 60 seconds, rinsed with water and then retained the blocks intraorally for 4 hours.
  • Percent mineral recovery for each enamel block was calculated as the ratio of the changes in enamel microhardness due to treatment (remineralization or remin.) and sucrose challenge (demineralization or demin.).
  • Toothpaste II of the general formula of Toothpaste I, except that there was absent within Toothpaste II any fluoride ion or casein glycomacropeptide.
  • Table II The remineralization efficacy results for Toothpaste I and the placebo Toothpaste II are summarized in Table II, below.

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Claims (14)

  1. Mehrkomponenten-Antikaries-Zahnpflegezusammensetzung, die eine erste Zahnpflegekomponente, die eine Fluoridion freisetzende Verbindung enthält, und eine zweite Zahnpflegekomponente umfasst, die Caseinglykomakropeptidverbindung enthält, wobei die Komponenten vor Gebrauch physikalisch getrennt sind und bei Kombination nach Auftragung auf die Zähne verstärkte Remineralisierung des Zahnschmelzes liefern.
  2. Mehrkomponenten-Zahnpflegezusammensetzung nach Anspruch 1, bei der die Fluoridionverbindung eine wasserlösliche Fluoridverbindung ist.
  3. Mehrkomponenten-Zahnpflegezusammensetzung nach Anspruch 2, bei der die wasserlösliche Fluoridverbindung Natriumfluorid ist.
  4. Mehrkomponenten-Zahnpflegezusammensetzung nach Anspruch 1, bei der die Caseinglykomakropeptidverbindung ein kappa-Caseinoglykomakropeptid, ein kappa-Caseinoglykopeptid oder ein desialiniertes Derivat derselben ist.
  5. Mehrkomponenten-Zahnpflegezusammensetzung nach Anspruch 1, bei der die erste Fluoridionverbindung enthaltende Zahnpflegekomponente etwa 0,025 Gew.% bis etwa 1 Gew.% der Fluoridionverbindung enthält.
  6. Mehrkomponenten-Zahnpflegezusammensetzung nach Anspruch 1, bei der die zweite Caseinglykomakropeptidverbindung enthaltende Zahnpflegekomponente etwa 2 bis etwa 15 Gew.% Caseinglykomakropeptidverbindung enthält.
  7. Mehrkomponenten-Zahnpflegezusammensetzung nach Anspruch 1, bei der die zweite Caseinglykomakropeptidverbindung enthaltende Zahnpflegekomponente etwa 8 bis etwa 12 Gew.% Caseinglykomakropeptidverbindung enthält.
  8. Verwendung einer Mehrkomponenten-Antikaries-Zahnpflegezusammensetzung, die eine erste Zahnpflegekomponente, die eine Fluoridion freisetzende Verbindung enthält, und eine zweite Zahnpflegekomponente umfasst, die Caseinglykomakropeptidverbindung enthält, wobei die Verbindungen vor Gebrauch physikalisch getrennt sind, zur Herstellung eines Medikaments, um verstärkte Remineralisierung des Zahnschmelzes zu liefern.
  9. Verwendung nach Anspruch 8, bei der die Fluoridionverbindung eine wasserlösliche Fluoridverbindung ist.
  10. Verwendung nach Anspruch 9, bei der die wasserlösliche Fluoridverbindung Natriumfluorid ist.
  11. Verwendung nach Anspruch 8, bei der die Caseinglykomakropeptidverbindung ein kappa-Caseinoglykomakropeptid, ein kappa-Caseinoglykopeptid oder ein desialiniertes Derivat derselben ist.
  12. Verwendung nach Anspruch 8, bei der die erste Fluoridionverbindung enthaltende Zahnpflegekomponente etwa 0,025 Gew.% bis etwa 1 Gew.% der Fluoridionverbindung enthält.
  13. Verwendung nach Anspruch 8, bei der die zweite Caseinglykomakropeptidverbindung enthaltende Zahnpflegekomponente etwa 2 bis etwa 15 Gew.% Caseinglykomakropeptidverbindung enthält.
  14. Verwendung nach Anspruch 8, bei der die zweite Caseinglykomakropeptidverbindung enthaltende Zahnpflegekomponente etwa 8 bis etwa 12 Gew.% Caseinglykomakropeptidverbindung enthält.
EP98946075A 1997-09-22 1998-09-16 Fluorid enthaltende zahnpasten mit verbesserte wirksamkeit Expired - Lifetime EP1017362B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/935,367 US5853704A (en) 1997-09-22 1997-09-22 Fluoride dentifrices of enhanced efficacy
US935367 1997-09-22
PCT/US1998/019287 WO1999015142A1 (en) 1997-09-22 1998-09-16 Fluoride dentifrices of enhanced efficacy

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EP1017362A1 EP1017362A1 (de) 2000-07-12
EP1017362B1 true EP1017362B1 (de) 2002-02-20

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US (1) US5853704A (de)
EP (1) EP1017362B1 (de)
JP (1) JP2001517610A (de)
CN (1) CN1189154C (de)
AR (1) AR017134A1 (de)
AT (1) ATE213402T1 (de)
AU (1) AU738420B2 (de)
BR (1) BR9812363B1 (de)
CA (1) CA2303370C (de)
CO (1) CO4970709A1 (de)
DE (1) DE69803937T2 (de)
DK (1) DK1017362T3 (de)
ES (1) ES2173619T3 (de)
PT (1) PT1017362E (de)
WO (1) WO1999015142A1 (de)
ZA (1) ZA988593B (de)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001525853A (ja) * 1997-05-19 2001-12-11 コルゲート・パーモリブ・カンパニー フッ化物を用いない歯の再石灰化
US6110446A (en) * 1998-10-05 2000-08-29 Colgate Palmolive Company Dual component antiplaque and tooth whitening composition
EP1062876A1 (de) * 1999-02-25 2000-12-27 Societe Des Produits Nestle S.A. Caseinoglycomacropeptide als Kalzifizierungsmittel
US6372198B1 (en) 2000-09-14 2002-04-16 Joseph M. Abbate Dentifrice for the mineralization and remineralization of teeth
US6482396B1 (en) 2001-05-15 2002-11-19 Campina Melkunie B.V. Methods for treating or preventing diseases of the oral cavity
EP1342467A1 (de) * 2002-03-04 2003-09-10 Société des Produits Nestlé S.A. Stabilisieren von wässrigen cGMP Formulierungen
US7860080B2 (en) * 2002-03-06 2010-12-28 Telefonaktiebolaget Lm Ericsson (Publ) Service provisioning in telecommunications system comprising call control service capability servers
US20040101494A1 (en) 2002-11-26 2004-05-27 Scott Douglas Craig Chewable solid unit dosage forms and methods for delivery of active agents into occlusal surfaces of teeth
WO2007092811A2 (en) * 2006-02-07 2007-08-16 Whitehill Oral Technologies, Inc. Sialagogue based oral care products
US20080076445A1 (en) * 2006-08-18 2008-03-27 Aaron Hollander Enterprise scheduling system
GB0723523D0 (en) * 2007-11-30 2008-01-09 Glaxo Group Ltd Novel use
JP2010047494A (ja) * 2008-08-20 2010-03-04 Gc Corp 歯牙塗布用組成物
KR20140005868A (ko) 2010-08-24 2014-01-15 세이프화이트 엘엘씨 치아에 흰색 외관을 제공하기 위한 방법 및 재료
WO2012078137A1 (en) 2010-12-07 2012-06-14 Colgate-Palmolive Company Apparatus for conducting oral care experiments and method of forming and using the same
CN105377218B (zh) * 2013-07-19 2019-06-11 荷兰联合利华有限公司 再矿化口腔护理产品
CN107743386A (zh) 2015-06-05 2018-02-27 荷兰联合利华有限公司 口腔护理装置
US10758474B2 (en) 2018-05-30 2020-09-01 Radius Corporation Organic toothpaste
US11058628B2 (en) 2018-05-30 2021-07-13 Radius Corporation Organic toothpaste

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4487757A (en) * 1981-12-28 1984-12-11 Colgate-Palmolive Company Dispensing container of toothpaste which effervesces during toothbrushing
US4687663B1 (en) * 1983-03-01 1997-10-07 Chesebrough Ponds Usa Co Dental preparation article and method for storage and delivery thereof
CH671879A5 (de) * 1987-02-26 1989-10-13 Nestle Sa
JP2673828B2 (ja) * 1989-04-19 1997-11-05 雪印乳業株式会社 κ―カゼイングリコマクロペプチドの製造法
CH681543A5 (de) * 1990-04-27 1993-04-15 Nestle Sa
US5227154A (en) * 1991-08-22 1993-07-13 The University Of Melbourne Phosphopeptides for the treatment of dental calculus
CH684773A5 (fr) * 1992-12-28 1994-12-30 Nestle Sa Composition alimentaire anti-cariogène.
ATE206877T1 (de) * 1995-06-16 2001-11-15 Nestle Sa Fluorierte kasein-mizellen

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DE69803937T2 (de) 2002-10-17
CO4970709A1 (es) 2000-11-07
US5853704A (en) 1998-12-29
CA2303370C (en) 2008-08-12
CN1189154C (zh) 2005-02-16
CA2303370A1 (en) 1999-04-01
ATE213402T1 (de) 2002-03-15
AU738420B2 (en) 2001-09-20
WO1999015142A1 (en) 1999-04-01
AU9317098A (en) 1999-04-12
CN1271268A (zh) 2000-10-25
DE69803937D1 (de) 2002-03-28
EP1017362A1 (de) 2000-07-12
ZA988593B (en) 2000-03-22
PT1017362E (pt) 2002-08-30
JP2001517610A (ja) 2001-10-09
DK1017362T3 (da) 2002-06-17
ES2173619T3 (es) 2002-10-16
BR9812363B1 (pt) 2010-12-14
AR017134A1 (es) 2001-08-22
BR9812363A (pt) 2000-09-19

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